To better understand how visual acuity (VA) changes over a long-term period (≥10 years) in treatment-naïve patients with Leber hereditary optic neuropathy (LHON) using eyes from the Case Record Survey-2 (CRS-2; NCT02796274).

After onset of symptoms (OoS), the typical course of LHON consists of sharply worsening VA in the first year with minimal change once the chronic phase is reached. Some patients can, however, experience spontaneous partial recovery.  Age at OoS and mitochondrial DNA (mtDNA) mutation are thought to significantly impact disease course.

Retrospective clinical data were extracted from case records of treatment-naïve LHON patients aged ≥12 years, with a confirmed m.11778G>A, m.14484T>C or m.3460G>A mtDNA mutation, OoS after 1999, and ≥2 VA assessments within 5 years of OoS. Baseline visit: first VA assessment after OoS. At baseline, all eyes in this analysis were in the subacute/dynamic phase (≤1 year after OoS).

A total of 32 eyes had follow-up data of ≥10 years at last visit from baseline; median (Q1–Q3) VA at baseline was 0.90 (0.22–1.49) logMAR. The distribution of age at OoS (years) was: <15: 31.3% (n=10/32); 15–35: 50.0% (n=16/32); >35: 18.8% (n=6/32) and the mtDNA distribution was: m.11778G>A: 75.0% (n=24/32); m.14484T>C: 18.8% (n=6/32); m.3460G>A: 6.3% (n=2/32). High inter- and intra-patient variability in VA trajectories was observed irrespective of age at OoS. Inter-patient variability was also observed irrespective of mtDNA mutation with high intra-patient variability evident in m.11778G>A eyes. This was difficult to assess in m.14484T>C and m.3460G>A eyes due to low numbers. Irrespective of mtDNA and age subgroups, VA changes were still observed deep into the chronic phase.

High inter- and intra-patient variability in longitudinal VA change over 10 years is apparent in treatment-naïve LHON, even in the chronic phase. These observations support individualized management, and continued follow-up assessment for patients with LHON.